The goal of the research is to gain increased biochemical and molecular understanding of subtypes of NMDA and dopamine receptors. These receptors may be important in understanding the pathophysiology and treatment of illnesses such as schizophrenia and substance abuse, in addition to understanding basic brain processes. The initial focus will be on conotoxins, peptide ligands from the marine snail, I which represent novel tools for studying NMDA and dopamine receptors. One family of conotoxins, known as "conantokins" appears to have specificity for distinct developmental subtypes of NMDA receptors. Brain slice preparations, autoradioraphic techniques, brain mRNA injected oocytes and crosslinking techniques will be used to explore this hypothesis. A second family of conotoxins appears to target D2 dopamine receptors. These toxins will be purified, biochemically characterized and their receptor specificity determined. Molecular genetic techniques will be used to isolate D2 receptor-targeted peptide genes and define additional D2-specific conotoxin homologs.